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@ARTICLE{Bhardwaj:153230,
      author       = {M. Bhardwaj$^*$ and K. Weigl$^*$ and K. Tikk$^*$ and T.
                      Holland-Letz$^*$ and P. Schrotz-King$^*$ and C. H. Borchers
                      and H. Brenner$^*$},
      title        = {{M}ultiplex quantitation of 270 plasma protein markers to
                      identify a signature for early detection of colorectal
                      cancer.},
      journal      = {European journal of cancer},
      volume       = {127},
      issn         = {0959-8049},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2020-00263},
      pages        = {30 - 40},
      year         = {2020},
      note         = {#EA:C120#LA:C120#},
      abstract     = {Blood-based protein biomarker signatures might be an
                      alternative or supplement to existing methods for early
                      detection of colorectal cancer (CRC) for population-based
                      screening. The objective of this study was to derive a
                      protein biomarker signature for early detection of CRC and
                      its precursor advanced adenoma (AA). In a two-stage design,
                      270 protein markers were measured by liquid
                      chromatography/multiple reaction monitoring/mass
                      spectrometry in plasma samples of discovery and validation
                      sets. In the discovery set consisting of 100 newly diagnosed
                      CRC cases and 100 age- and sex-matched controls free of
                      neoplasm at screening colonoscopy, the algorithms predicting
                      the presence of early- or late-stage CRC were derived by
                      Lasso regression and .632 + bootstrap. The prediction
                      algorithms were then externally validated in an independent
                      validation set consisting of participants of screening
                      colonoscopy including 56 participants with CRC, 99 with AA
                      and 99 controls without any colorectal neoplasms. Three
                      different signatures for all-, early- and late-stage CRC
                      consisting of five-, three- and eight-protein markers were
                      obtained in the discovery set with areas under the curves
                      (AUCs) after .632 + bootstrap adjustment of 0.85, 0.83 and
                      0.96, respectively. External validation in the
                      representative screening population yielded AUCs of 0.79
                      $(95\%$ CI, 0.70-0.86), 0.79 $(95\%$ CI, 0.66-0.89) and 0.80
                      $(95\%$ CI, 0.70-0.89) for all-, early- and late-stage CRCs,
                      respectively. The three-marker early-stage algorithm yielded
                      an AUC of 0.65 $(95\%$ CI, 0.56-0.73) for detection of AA in
                      the validation set. Although not yet competitive with
                      available stool-based tests for CRC early detection, the
                      identified proteins may contribute to the development of
                      powerful blood-based tests for early detection of CRC and
                      its precursors AAs.},
      cin          = {C120 / C070 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)C120-20160331 / I:(DE-He78)C070-20160331 /
                      I:(DE-He78)HD01-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31972396},
      doi          = {10.1016/j.ejca.2019.11.021},
      url          = {https://inrepo02.dkfz.de/record/153230},
}